Project Summary HIV infection remains a major challenge for global health, leading to over 2 million new infections per year and accounting for 1.5 million deaths per year. Antiretroviral therapy has significantly improved morbidity and mortality, but requires life-long treatment. This is due to the presence of latent viral reservoirs, which cause the rapid recurrence of viremia upon treatment interruption. Better understanding of how to prevent the complications of infection and limit the formation of the viral reservoir could offer insights for the development of novel therapeutic strategies. Natural killer (NK) cells may play a critical role in the control of HIV infection. However, our understanding of how NK cells contribute to delayed disease progression or lower HIV reservoir is limited. Thus, I propose using CyTOF to deeply profile the NK cell repertoire in HIV-infected subjects to identify NK cell subpopulations associated with delayed disease progression and lower HIV persistence. To establish their mechanistic role, I will test the ability of such subpopulations to suppress HIV replication and kill HIV-infected cells in vitro. My goal is to identify NK cell subpopulations with increased ability to fight HIV. This knowledge will be critical for the development new therapies, which could combine pharmacological and immunological approaches to achieve a functional cure. I am currently a fellow in Dr. Catherine Blish's lab in the Division of Infectious Diseases at Stanford University and I am in the process of being promoted to a full time Instructor position. Stanford University offers an outstanding scientific environment, where all the resources necessary to the success of this project are made available to me. My long-term goal is to become an independent physician-scientist, with a research focus in HIV. I aim to establish a research program focused on immune correlates of disease and translate these findings into novel therapeutic strategies. To achieve this goal I have designed a tailored career development plan, which encompasses both formal an informal training. This training will enhance my expertise in immunology and statistics/epidemiology. Informal training in these topics will be provided by my mentor, Dr. Catherine Blish, my co-mentors, Drs. Mark Davis and Julie Overbaugh, and by the rest of my advisory committee, Drs. Susan Holmes and Julie Parsonnet. With their guidance, I will complete the proposed project, submit research manuscripts, obtain further funding, and obtain an independent research position.